Hepatic ischemia-reperfusion increases vascular endothelial growth factor and cancer growth in rats.

BACKGROUND: In liver surgery, the hepatic pedicle often is clamped to reduce blood loss, and later unclamped, representing hepatic ischemia and reperfusion (I/R) with induction of hypoxia. Vascular endothelial growth factor (VEGF) expression reportedly is induced by hypoxia; further, some cancer cells express the VEGF receptor (flt-1, flk-1/KDR). We hypothesized that I/R-induced VEGF expression could enhance growth of microscopic tumor via VEGF receptors on tumor cells, thus promoting liver metastasis in a rat model. MATERIALS AND METHODS: Time-dependent VEGF expression in liver and plasma was determined by enzyme-linked immunosorbent assay in rats subjected to 60 min of 70% hepatic I/R (I/R group). Other rats given an intrasplenic inoculation of a rat colon adenocarcinoma cell line (RCH-H4) were divided 3 days later into three groups: group A, untreated; group B, sham operation; group C, 70% I/R for 60 min. Liver metastasis was evaluated on day 14. Expression of flt-1 and flk-1/KDR was examined in RCN-H4 cells, and effects of exogenous VEGF on RCN-H4 cell proliferation were determined by MTT assays. RESULTS: Hepatic VEGF expression increased significantly in the I/R group compared to the control group. Liver metastasis was more extensive in group C than in groups A and B. RCN-H4 cells expressed flt-1 and flk-1/KDR, while exogenous VEGF increased RCN-H4 cell proliferation. CONCLUSION: Hepatic ischemia reperfusion leads to induction of VEGF and this is associated with increased tumor burden in an animal model of colon cancer metastasis.

Edaravone reduces ischemia-reperfusion injury mediators in rat liver.

BACKGROUND: In hepatic ischemia-reperfusion (I/R) injury, oxidative stress both directly injures the liver and promotes an inflammatory reaction by up-regulating various inflammatory mediators. We investigated whether edaravone, a new hydroxy radical scavenger, could reduce hepatic I/R injury including expression of inflammatory mediators such as cytokines and adhesion molecules. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to 30 min of partial hepatic pedicle clamping (70%) followed by reperfusion. Just after initiation of reperfusion and again 1 h later, edaravone was administered intraportally. After reperfusion hepatic lipid peroxidation was measured by thiobarbituric acid assay, and hepatic injury was quantified by measuring hepatic enzymes in plasma. We serially quantified hepatic expression of mRNAs for tumor necrosis factor (TNF)-alpha and E-selectin, and histologically examined E-selectin expression and neutrophil accumulation. RESULTS: In the edaravone group, hepatic lipid peroxidation and hepatic enzyme leakage were significantly less than in the saline group. Hepatic expression of TNF-alpha and E-selectin mRNAs was significantly lower in the edaravone than the saline group, at 2 h after initiation of reperfusion. Histologically, E-selectin immunoreactivity and neutrophil accumulation were less evident in hepatic sections from the edaravone group. CONCLUSIONS: Edaravone reduced hepatic I/R injury by minimizing oxidative stress, and inhibited subsequent injurious inflammation by reducing expression of inflammatory cytokines and adhesion molecules.

[A 65-year-old man with liver metastases after lung cancer resection that responded to concomitant use of gemcitabine and carboplatin].

A 65-year-old male with liver metastases after lung cancer resection was treated with five courses of chemotherapy consisting of gemcitabine (GEM) 1,000 mg/m2 (day 1, 8, every 4 weeks) plus carboplatin (CBDCA) AUC 6 (day 1, every 4 weeks). A partial response (PR) was achieved, his symptoms abated and his quality of life(QOL) improved. Although bone marrow suppression was observed as a side effect, it was within the tolerable range and did not interfere with therapy. This approach may be worth considering as a first-line anti-cancer chemotherapy for recurrence lung cancer.

Retroperitoneal laparoscopic management of a lymphocele after abdominal aortic surgery: a case report.

A retroperitoneal lymphocele is a rare complication of abdominal aortic surgery. We present a case of 77-year-old man who developed a retroperitoneal lymphocele 14 days after undergoing graft replacement for an abdominal aortic aneurysm. Paracentesis showed a white and turbid fluid that was determined to be chyle. Conservative therapy, including percutaneous drainage, fasting, and total parenteral nutrition, was unsuccessful. Retroperitoneal laparoscopic ligation of the leaking lymphatics was performed on postoperative day 33. The postoperative course was satisfactory. The laparoscopic approach to retroperitoneal lymphocele treatment after abdominal aortic repair is a safe and minimally invasive therapeutic method.

[A case of advanced gastric cancer with peritonitis carcinomatosa resected with intraperitoneal chemotherapy based on chemosensitivity test with ascites].

The patient was a 57-year-old man who developed obstructive jaundice and pancreatitis. He was diagnosed with peritonitis carcinomatosa from gastric cancer, and the cancers were unresectable at first laparotomy. We gathered the accumulated ascites and examined the fluid by chemosensitivity test. Some anti-cancer drugs were selected based on the test results of test, and four cycles of modified PMUE therapy (CDDP ip, MMC iv, ETP po, UFT-E po) were performed. This chemotherapy proved very effective, and the cytodiagnostic malignancy with ascites changed from class V to II before and after chemotherapy. Following chemotherapy, a re-laparotomy was performed and a curability B operation could be undertaken. He survived for 17 months after the first laparotomy, but died of extra-peritoneal recurrence in the pelvic cavity. Treatment of advanced gastric cancers with peritonitis carcinomatosa is very difficult, because none of the various therapies (operation, chemotherapy, hyperthermia etc.) can completely control dissemination. It is very effective when the chemosensitivity of individual cancers is clear before chemotherapy. The current chemosensitivity test with ascites is still technically incomplete, but it may contribute to improved treatment of cancers with peritonitis carcinomatosa in the future.

Giant mediastinal bronchial artery aneurysm mimicking benign esophageal tumor: a case report and review of 26 cases from literature.

Mediastinal bronchial artery aneurysm is rare but potentially life-threatening, and requires prompt treatment to avert rupture with catastrophic results. A 78-year-old man was referred to our hospital with a benign esophageal tumor, which appeared as an extrinsic, extramucosal filling defect on an esophagogram. Chest computed tomography and selective bronchial arteriography led to a definitive diagnosis of mediastinal bronchial artery aneurysm. Aneurysmectomy and closure of the ostia of both the afferent and efferent bronchial arteries was performed via standard posterolateral thoracotomy. Postoperative course was uneventful, and the patient was discharged on the seventh postoperative day.

Intermittent hepatic ischemia-reperfusion minimizes liver metastasis in rats.

BACKGROUND: Surgical stresses, including hepatic ischemia-reperfusion (I/R), promote cancer growth and metastasis. We have reported that continuous hepatic I/R increases liver damage and promoted liver metastasis from colon cancer, whereas intermittent I/R causes less liver damage. We therefore examined whether intermittent I/R could reduce liver metastasis in a rat model. MATERIALS AND METHODS: Adult male Fischer rats was divided between three groups: group A (control), which received laparotomy for 120 min with no liver ischemia; group B (continuous I/R), which received 60 min of 70% partial liver ischemia followed by 60 min of reperfusion; and group C (intermittent I/R), which received 15 min of 70% ischemia and 15 min of reperfusion, repeated four times. Just before closing the abdomen, all animals were inoculated intrasplenically with rat colon adenocarcinoma cells (RCN-H4). Tumor nodules on the liver surface were counted 3 weeks later. In addition, expression of E-selectin mRNA in liver was examined at 1, 3, and 6 h after completing I/R by a reverse transcription-polymerase chain reaction. RESULTS: Continuous I/R (B) greatly promoted liver metastasis in both ischemic and nonischemic liver lobes, whereas intermittent I/R (C) showed significantly fewer metastasis than group B in both lobes. Significantly less E-selectin mRNA was expressed in group C than in group B. CONCLUSIONS: Intermittent I/R limits expression of E-selectin mRNA and liver metastasis. Intermittent hepatic I/R is less stressful than continuous I/R, minimizing liver metastasis by colon cancer cells through avoidance of E-selectin up-regulation.

Tolerance to intermittent ischemia of damaged rat liver by thioacetamide.

BACKGROUND/AIMS: Tolerance of damaged rat livers for intermittent ischemia was assessed. Clinically, tolerance of operative ischemia by diseased livers, long thought minimal, is being reexamined. METHODOLOGY: A rat model using 0.04% thioacetamide-induced liver damage followed by pedicle occlusion was used to study partial hepatic ischemia in injured livers in terms of survival, hepatic tissue blood flow, beta-ATP content, liver enzymes and histology. Prior to continuous ischemia (150 min) or intermittent ischemia (alternating every 15 min with reperfusion for 10 cycles) animals were divided into mild (B) and severe (A) thioacetamide-induced injury groups according to the hepatic clearance rate of indocyanine green from plasma. RESULTS: The survival rates for 1 week after intermittent ischemia were 43%, 77%, and 93% in groups A and B and in controls (group C), respectively. No group A or B animals receiving continuous ischemia survived. Hepatic tissue blood flow and liver beta-ATP levels in serum were significantly higher in group A than in other groups. Marked damage also was observed histologically in group A. CONCLUSIONS: Intermittent liver circulation blockage may be relatively safe in a damaged liver, but a more severe degree of damage predisposes to serious ischemia-reperfusion injury.

Hepatic ischemia-reperfusion promotes liver metastasis of colon cancer.

BACKGROUND: The effects of hepatic ischemia/reperfusion (I/R) on liver metastasis have not been fully examined. We examined hepatic I/R and liver metastasis of colorectal cancer in a rat model; we also quantitated expression of E-selectin (ELAM-1) mRNA after I/R. MATERIALS AND METHODS: Rats underwent 30 or 60 min of 70% partial hepatic ischemia. After 60 min of reperfusion, rat colon adenocarcinoma cells (RCN-H4) were inoculated intrasplenically. The number of tumor nodules on the liver surface was determined 3 weeks later. Expression of E-selectin mRNA was determined at 1, 3, and 6 h after ischemia by quantitative RT-PCR. RESULTS: Hepatic I/R promoted liver metastasis of RCN-H4 and induced the expression of E-selectin mRNA in both clamped and unclamped liver lobes. The number of tumor nodules and the expression of E-selectin mRNA after 60 min of ischemia was greater than that after 30 min. CONCLUSIONS: Hepatic I/R, especially with a long duration of ischemia, induces expression of E-selectin and promotes liver metastasis of colon cancer in rats.

[A gastric cancer patient with marked para-aortic lymph node metastasis surviving more than 10 years after aggressive operation and repeated EAP chemotherapy].

The high incidence of side effects for EAP (etoposide, adriamycin, cisplatin) combination chemotherapy led to the recent decline in its use. However, we report herein the long-term disease-free survival of a woman following postoperative EAP therapy. A 57-year-old woman was referred to our hospital because of general malaise. X-ray and endoscopic examination revealed a Borrmann type 3 gastric cancer. Preoperative computed tomography and ultrasonography revealed multiple para-aortic lymph node swellings. The patient simultaneously underwent subtotal gastrectomy and splenectomy, and complete para-aortic lymph node dissection. Histopathological tests revealed that the tumor was a poorly differentiated adenocarcinoma with 35 metastatic para-aortic lymph nodes. The patient was treated with 2 cycles of EAP therapy. After discharge, swelling in one para-aortic lymph node was detected. Following three subsequent cycles of EAP therapy, the swollen lymph node disappeared and the patient has remained disease free for 10 years. This case illustrates that aggressive surgery followed by repeated courses of EAP therapy can produce excellent clinical outcomes.

Neutrophil elastase inhibitor reduces hepatic metastases induced by ischaemia-reperfusion in rats.

OBJECTIVE: To investigate the possibility in rats that ONO-5046 Na, a new recombinant inhibitor of neutrophil elastase, can reduce hepatic metastases induced by ischaemia-reperfusion. DESIGN: Laboratory experimental study. SETTING: Research laboratory, Japan. SUBJECTS: Male Fischer rats. INTERVENTIONS: Rats underwent 60 min of 70% partial hepatic ischaemia, after which rat colon adenocarcinoma cells (RCN-H4) were injected into the spleen. The animals were divided into two test groups and a control group. One group was given ONO-5046 Na intravenously at 10 mg/kg/hour. A second group was given a saline solution for the same period, while the controls were not made ischaemic. MAIN OUTCOME MEASURES: Three weeks after inoculation, the number of tumour nodules on the liver surface was counted. The anti-cancer effect of ONO-5046 Na was measured by monotetrazolium assay. RESULTS: Hepatic ischaemia-reperfusion increased the number of liver metastases of RCN-H4 in both clamped and unclamped hepatic lobes. ONO-5046 Na significantly inhibited this in unclamped lobes, but had no anti-cancer effect. CONCLUSION: Neutrophil elastase may have an important role in increasing haematogenous liver metastases by ischaemia-reperfusion, particularly in unclamped lobes.